Background & Aims

The PIEZO2 ion channel is critical for transducing light touch into neural signals but is not considered necessary for transducing acute pain in humans (Szczot et al., 2018; Nagi et al., 2019). Here, we discovered an exception – a form of mechanical pain evoked by hair pulling.

Methods

To address this, first, we conducted psychophysical experiments by testing a range of pulling forces on single hairs in control participants, individuals with PIEZO2 deficiency syndrome, and individuals with A? deafferentation. We then performed a preferential ischemic nerve block to investigate the contributions of primary afferents to hair-pulling pain. Next, we used in vivo electrophysiological recordings (microneurography) from single mechanoreceptive cutaneous neurons to investigate the neural coding of single hair pulls. Finally, using functional imaging combined with pharmacological mapping approach, we tested hair pull pain in mice with a conditional knockout of Piezo2.

Results

We found hair-pulling elicits a distinct, low-threshold pain sensation associated with a specific urge-to-move behavior. Interestingly, individuals with PIEZO2 deficiency syndrome had a deficit in pain perception to hair-pulling stimuli. Hair-pulling pain was abolished in the condition of blocked A? fibers – a finding confirmed in selective A? deafferented individuals who did not perceive hair-pulling stimuli as painful. Single?unit axonal recordings revealed that a class of cooling?responsive myelinated nociceptors in human skin is selectively tuned to painful hair?pull stimuli. Furthermore, using a pharmacological mapping approach, we have confirmed that these hair?pull coding fibers belonged exclusively to a transcriptomically defined class of nociceptors and that Piezo2 is critical for hair?pulling response of these neurons.

Conclusions

These findings demonstrate that a specialized class of rapidly conducting PIEZO2?dependent
nociceptors associated with hair follicles serves as evolutionarily conserved mediators of hair?pull pain.

References

Szczot, M., Liljencrantz, J., Ghitani, N., Barik, A., Lam, R., Thompson, J.H., Bharucha?Goebel, D., Saade, D., Necaise, A., Donkervoort, S., et al. (2018). PIEZO2 mediates injury?induced tactile pain in mice and humans. Sci Transl Med 10. 10.1126/scitranslmed.aat9892.
Nagi, Saad S., et al. “An ultrafast system for signaling mechanical pain in human skin.” Science advances 5.7 (2019): eaaw1297.

Presenting Author

Otmane Bouchatta

Poster Authors

Otmane Bouchatta

PhD

Linköping University

Lead Author

Topics

  • Mechanisms: Biological-Systems (Physiology/Anatomy)